There are microneedles for the pharmaceutical technology for improving absorption rates of drugs that are extremely low in permeability to the stratum corneum layer of skin. Microneedles are needles that are miniaturized to such an extent that one does not feel pain even if the skin is punctured with them. The microneedles generally have a length of 1 mm or less.
These microneedles have similar hollow structures to injection needles. They are of a type in which a drug solution is injected, or are made of a biodegradable polymer such as polylactic acid. Furthermore, dissolving microneedles using a water-soluble polymer substance as a base have also been developed. That is, an objective substance is retained in the water-soluble substance as the base. After inserted into skin, the base is dissolved by water in the skin, so that the objective substance may be transdermally administered.
For example, Patent Document 1 discloses that a self-dissolving microneedle is formed using, as a base, a polymer substance which is bio-soluble and thread-forming. Patent Document 2 discloses that a microneedle is divided into a part to be inserted into a living body and a pressing part, and that an objective substance is retained only in the part to be inserted into the living body in order to improve bioavailability of the objective substance contained in the microneedle.
Also, Patent Documents 1 and 2 disclose a sheet-shaped microneedle preparation administration member, in which the plurality of microneedles are formed on a platform such as a patch sheet. Use of the microneedle preparation administration member makes it possible to apply a microneedle preparation to a wide area of skin with less labor.
In the present specification, unless otherwise stated, the microneedle preparation means a self-dissolving transdermal absorption preparation which retains a drug, and self-dissolves when inserted into skin, thereby allowing the skin to absorb the drug. Unless otherwise stated, the microneedle preparation administration member means a microneedle preparation administration member, in which the plurality of microneedle preparations are formed on a platform. Specific examples of the microneedle preparation administration member include a microneedle (preparation) sheet, a microneedle (preparation) patch, a microneedle (preparation) chip, a microneedle (preparation) array sheet, a microneedle (preparation) array patch, a microneedle (preparation) array chip and the like.
Patent Document 3 discloses that by using a microneedle preparation for prevention or treatment of skin aging, or treatment of skin scars, long-term stability of an effective component is achieved, and that this allows a physician or a patient himself or herself to administer the effective component to the site of action in the skin easily, efficiently and equally, so that one may benefit from advantages such as alleviation of skin scars and rejuvenation of skin in early stage after the treatment.
However, when the microneedle preparation is used for prevention or treatment of skin aging, or treatment of skin scars, the necessity for optimization of delivery depth of the objective substance has been revealed. For example, in case of providing treatment with the use of a microneedle preparation containing bFGF, melanocytes distributed in a basal layer in epidermis of skin, that are on an administration route when the microneedle preparation is administered directly into dermis in a transdermal manner, are stimulated, and pigmentation as a side effect is caused. In order to prevent the reaction, it is preferred to realize a state in which the objective substance is absent in the vicinity of a basal layer in epidermis and a papillary layer in dermis while an only objective substance-containing portion is inserted and placed in a reticular layer in dermis or in a sub-papillary layer in dermis which are at the targeted depth in the dermis.
The microneedle has highest insertion ability when pressed while standing it upright, right angle to skin surface. Therefore, a development of an administration apparatus, which presses a microneedle preparation from direction perpendicular to skin has been made.
For example, Patent Document 4 discloses an instrument for administration of a microneedle preparation, the instrument comprising: a tubular cylinder; and a piston for supporting a microneedle preparation administration member within the cylinder, wherein the piston is pressed by a finger to move the microneedle preparation in outlet direction of the cylinder, so that it is brought into press contact with a skin surface. Furthermore, Patent Document 5 discloses an instrument for administration of a microneedle preparation, the instrument comprising: a guide tube; a support rod for supporting the microneedle preparation within the guide tube; and means for driving the support rod toward skin.
There are irregularities on a surface of a body, and irregularities on the face are very noticeable. When a large size microneedle preparation administration member is applied to a surface with irregularities, microneedles which are not pressed perpendicularly thereto increase, resulting in the occurrence of many insertion failures. When the microneedle preparation is applied to an area with irregularities, the area to be applied is divided into administration sites, each of which may be regarded as flat, and then it is required to press the microneedle preparation administration member from an optimal direction for each divided administration site.
Considering an embodiment for actually providing treatment, the size of the microneedle preparation administration member would not be enlarged to the area which may be regarded as flat on the surface of the body. When the area to be applied is larger than that, an operation of sequentially administering a plurality of microneedle preparation administration members is required.
When a plurality of microneedle preparation administration members are sequentially administered, duplicate administration to skin causes overdosing of bFGF, resulting in that a predetermined effect is not obtained, or that the probability of side effects such as inducing pigmentation becomes higher. In this case, particularly in the case of a circular or elliptical microneedle preparation administration member, avoiding duplication inevitably generates a part where administration would not be made contrary to that, so that an optimal therapeutic effect would not be expected.
Since a large number of melanocytes are distributed in an epidermal layer of skin, if a growth factor such as bFGF is administered to the epidermal layer or nearby it, the pigment producing melanocytes are stimulated to produce melanin thus causing pigmentation as the side effect. The bFGF affects a lot of fibroblasts distributed in a dermal layer of skin and let them proliferate to exhibit a regeneration effect of the skin. Therefore, a seemingly paradoxical objective that bFGF surely be delivered to the dermal layer, need to be realized. Furthermore, an area of skin on which regeneration treatment is to be conducted is specified, and it is desired that the treatment is evenly conducted through the area. Therefore, bFGF microneedle preparation administration members need to be administered sequentially without causing duplicate administration within a specified area.
In general, it takes several hours for the self-dissolving microneedle transdermal absorption preparation to dissolve completely after it is inserted into the skin. Therefore, it is required that the microneedle preparation administration member be pressed for several tens of minutes after administration. However, the administration process that requires long time causes delay in treatment, there is a problem in practical use.